Tebentafusp for Soft Tissue Sarcoma

Overseen By SARC Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sarcoma Alliance for Research through Collaboration

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Cardiac disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: Approximately 5.5 months

47 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of tebentafusp for individuals with clear cell sarcoma, a type of cancer that cannot be surgically removed or has metastasized. Researchers aim to determine if this treatment can manage the disease and improve patient outcomes. Participants will receive tebentafusp through an IV infusion on a set schedule to assess its effects. Those unable to receive tebentafusp will receive an alternative treatment chosen by their doctor. The trial seeks individuals diagnosed with unresectable or metastatic clear cell sarcoma who have shown disease progression. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in cancer care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on systemic steroid therapy or other immunosuppressive medications, as these may interfere with the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tebentafusp has been studied in various clinical settings, providing important information about its safety. A detailed safety review of 410 patients found that tebentafusp is generally well-tolerated. While some patients experienced side effects, these were usually manageable.

Additionally, real-world data from patients with metastatic uveal melanoma (a type of eye cancer) indicates that tebentafusp is safe for both those who have had previous treatments and those who are new to treatment. This real-world evidence supports findings from controlled clinical studies.

It is important to note that this treatment is in a phase II trial, indicating it has already shown some safety in earlier studies. However, ongoing trials continue to evaluate its safety and effectiveness for other conditions, such as clear cell sarcoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sarcoma?

Tebentafusp is unique because it specifically targets cancer cells by engaging T-cell receptors to recognize and destroy tumor cells. Most treatments for soft tissue sarcoma involve traditional chemotherapy or radiation, which can affect healthy cells and lead to significant side effects. Tebentafusp offers a more targeted approach, potentially reducing those side effects and improving outcomes for patients. Researchers are excited about this treatment because it represents a novel way to harness the body's immune system to fight cancer more precisely.

What evidence suggests that this trial's treatments could be effective for soft tissue sarcoma?

Research has shown that tebentafusp may be a promising treatment for certain cancers. In studies with patients who have metastatic uveal melanoma, tebentafusp significantly improved survival rates. One study found that 63.6% of patients were still alive after one year, with an average survival time of 20 months. In this trial, eligible participants will receive tebentafusp, which targets specific proteins on cancer cells, helping the immune system recognize and attack them. Meanwhile, patients who are HLA-A*02:01-negative and ineligible for tebentafusp will receive treatment in a separate arm with the physician's choice of therapy. These results suggest that tebentafusp could help treat advanced cancers, like clear cell sarcoma, by possibly extending patients' lives. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with advanced clear cell sarcoma who are HLA-A*02:01 positive. They should be relatively stable (ECOG ≤2), have certain normal organ function tests, and measurable disease by scans. Those with Gilbert's disease can join, but there are exclusions not specified here.

Inclusion Criteria

I am HLA-A*02:01 positive.

I can perform daily activities with minimal assistance.

I have a tumor that can be measured on a scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly tebentafusp via IV infusion, with dose escalation from 20 mcg to 68 mcg over the first 15 days, followed by full dose administration

Approximately 5.5 months

Weekly visits for IV infusion

Radiographic Assessment

Radiographic assessment via CT or MR occurs every 6 weeks through 48 weeks, then every 9 weeks thereafter

48 weeks

Every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Tebentafusp

Trial Overview The study is testing Tebentafusp, a new treatment against physician's choice of therapy in participants with unresectable or metastatic clear cell sarcoma. It's an open-label Phase II trial, meaning both the researchers and participants know which treatment is being administered.

How Is the Trial Designed?

Group I: Tebentafusp Experimental Treatment 1 Intervention

Tebentafusp will be administered via IV infusion on Days 1, 8, and 15 of a 21-day cycle. Treatment on C1D1 will be 20mcg, treatment on C1D8 will be 30 mcg. After this initial dosing period, beginning at C1D15 and beyond, patients are eligible to receive the full dose of 68 mcg. This escalated dose administered at C1D15 will be the dose used for the remainder of the treatment period unless dose reduction is implemented for toxicity.

Group II: Physician's choice arm Active Control 1 Intervention

Patients who are HLA-A\*02:01-negative and ineligible to receive tebentafusp will be prospectively enrolled onto a separate study arm and treated with physicians' choice of treatment. They will also be radiographically assessed at the same schedule as patients treated with tebentafusp, if feasible, and kept on this treatment arm until progression of disease or unacceptable toxicity on the physicians' choice regimen.

Who Is Running the Clinical Trial?

Sarcoma Alliance for Research through Collaboration

Lead Sponsor

Trials

26

Recruited

2,000+

Royal Marsden NHS Foundation Trust

Collaborator

Trials

331

Recruited

10,150,000+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40680464/

Real-life data on tebentafusp in metastatic uveal ... 1-year OS rate was 63.6 %. Survival was significantly lower for patients with elevated LDH or extrahepatic metastases. Conclusion: Tebentafusp ...

2. jitc.bmj.com jitc.bmj.com/content/12/6/e009028

Long-term survival follow-up for tebentafusp in previously ... Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic ...

3. academic.oup.com academic.oup.com/oncolo/article/30/10/oyaf323/8268010

Concurrent local therapy extends clinical benefit of ... Tebentafusp has significantly improved overall survival in HLA-A*02:01+ mUM patients; however, clinical benefit remains modest with limited ...

4. ejcancer.com ejcancer.com/article/S0959-8049(25)00416-2/fulltext

Real-life data on tebentafusp in metastatic uveal ... Median progression-free survival (PFS) was 4 months (95 % CI 2.7–5.3), median OS was 20 months (95 % CI 15.3–24.6). 1-year OS rate was 63.6 %. Survival was ...

5. immunocore.com immunocore.com/investors/news/press-releases/detail/35/immunocore-presents-new-data-on-kimmtrak-tebentafusp-tebn-in-metastatic-cutaneous-mcm-and-uveal-melanoma-mum-at-the-2022-american-society-of-clinical-oncology-asco-annual-meeting

Immunocore presents new data on KIMMTRAK ... 58% of patients with any tumor increase were alive at 1-year, compared to 64% in the Phase 3 study in mUM. These data provide a rationale for a ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40938927/

Pooled Safety Analysis of 410 patients Purpose: We conducted an integrated safety analysis from three clinical studies of tebentafusp, a first-in-class ImmTAC bispecific T cell ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/761228Orig1s000MultidisciplineR.pdf

761228Orig1s000 MULTI-DISCIPLINE REVIEW Summary ... The safety of tebentafusp has been adequately characterized by data submitted from Study 202 and by supportive data submitted from other studies in the ...